Biomedical subjects

Junyan Gu

Publications and source records attributed to Junyan Gu.

8 recordsLinked to original sources

PubMed2007

Heart preservation using continuous ex vivo perfusion improves viability and functional recovery.

BACKGROUND: Cold static storage (CS) is a proven preservation method for heart transplantion, yet early postoperative graft dysfunction remains prevalent, so continuous perfusion (CP) during ex vivo transport may improve viability and function of heart grafts. METHODS AND RESULTS: Canine hearts underwent CP (n=9) or CS (n=9) for 6 h while intramyocardial pH was continuously monitored. Biopsies were assayed for ATP, caspase-3, malondialdehyde (MDA), and endothelin-1 (ET-1) levels at baseline, after preservation (t1), and after 1 h of blood reperfusion on a Langendorff model (t2). Functional recovery was determined at t2 by +dP/dt, -dP/dt, developed pressure, peak pressure and end-diastolic pressure. CP resulted in higher tissue pH and ATP stores and reduced caspase-3, MDA and ET-1 levels compared with CS at both t1 and t2. Post reperfusion recovery was significantly greater in CP vs CS for all myocardial functional parameters except end-diastolic pressure. Weight gain was significantly increased in CP vs CS at t1, but not at t2. CONCLUSIONS: Low-grade tissue acidosis and energy depletion occur during CS and are associated with oxidative injury and apoptosis during reperfusion. CP attenuates these biochemical and pathologic manifestations of tissue injury, together with improved myocardial recovery, despite mild, transient edema.

Adenosine Triphosphate↗

PubMed2006

Aprotinin shows both hemostatic and antithrombotic effects during off-pump coronary artery bypass grafting.

BACKGROUND: Hemostatic drugs are widely thought to be unnecessary and potentially detrimental in off-pump coronary artery bypass graft surgery (OPCABG), despite well-established use in on-pump surgery. In a randomized, prospective OPCABG trial, we assessed efficacy and safety of aprotinin through a comprehensive assessment of graft patency and hematologic function. METHODS: Sixty patients were randomly assigned to full-dose aprotinin or placebo. Heparin was titrated to a kaolin-based activated clotting time of greater than 300 seconds. Exclusionary criteria included creatinine greater than 2 mg/dL, conversion to on-pump CABG, and preoperative GPIIb/IIIa inhibition. Hematologic assessments were obtained preoperatively, at the end of surgery, and on days 1 and 3: mean platelet volume, thrombin generation (prothrombin fragment 1.2 assay), and aspirin resistance using a modified thrombelastography, whole blood aggregometry, 11-dehydro-thromboxane B2 levels, and flow cytometry. Thrombotic events were defined as postoperative myocardial infarction by electrocardiography or elevated troponin I, clinical stroke by examination and head computed tomography, and bypass graft failure by multichannel computed tomography angiography on day 5. RESULTS: Aprotinin was associated with a significant reduction in intraoperative and postoperative blood loss compared with placebo but had no effect on transfusion rates. Patients treated with aprotinin had significantly fewer thrombotic events (3% versus 23%, p < 0.05, Fisher's exact test) and less postoperative aspirin resistance (20% versus 46%, respectively, p < 0.05, Fisher's exact test). Postoperative prothrombin fragment 1.2 level was reduced by aprotinin use. CONCLUSIONS: Aprotinin reduced perioperative bleeding after OPCABG. Preserved aspirin sensitivity in the aprotinin group may explain the observed reduction in thrombotic events and might be related to the suppression of perioperative and transmyocardial thrombin formation.

Aprotinin↗

PubMed2005

Endothelial injury and acquired aspirin resistance as promoters of regional thrombin formation and early vein graft failure after coronary artery bypass grafting.

OBJECTIVE: The predominant mechanism of early graft failure after coronary artery bypass grafting remains in doubt. Aspirin administered in the initial hours after coronary artery bypass grafting improves graft patency, implicating prostanoid synthesis in the pathogenesis. We hypothesized that synergy between endothelial disruption in the venous conduit and aspirin resistance would cause vein graft failure. METHODS: Aspirin resistance, defined by diagnostic findings on at least two of three separate assays, was serially assessed in 225 patients undergoing off-pump coronary artery bypass grafting. Endothelial cell integrity was determined in surplus segments obtained from 408 vein grafts. The deposition of intraluminal thrombin within the vein was determined by comparing serum F1.2 levels between the coronary sinus and the aorta after grafting. Intraoperative blood flow in the grafts was measured with transit-time technology, and patency was assessed with electrocardiographically gated multichannel computed tomographic coronary angiography on day 5. Aspirin was the sole antithrombotic agent used during the study. RESULTS: Thrombosed grafts (16/408) showed more endothelial cell loss at the time of grafting than did those grafts that remained patent (10.8% +/- 21.5% vs 51.4% +/- 39.1% integrity, P < .01). Aspirin resistance occurred in 67 patients (30%). Graft thrombosis was associated with aspirin resistance (P < .04) and reduced endothelial integrity (P < .01). These factors coexisted in 14 of 16 grafts that failed and were associated with elevated coronary sinus F1.2 levels. CONCLUSION: Aspirin resistance and relatively compromised venous endothelial cell integrity together marked patients whose vein grafts failed within days after off-pump coronary artery bypass grafting. These observations form a basis for identifying patients at risk and developing approaches to prevent vein injury or to selectively intervene in high-risk circumstances.

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PubMed2005

Disruption of graft endothelium correlates with early failure after off-pump coronary artery bypass surgery.

BACKGROUND: Saphenous vein graft failure after coronary artery bypass surgery may be as high as 5% to 10% in the first postoperative week. We hypothesized that identifying damage sustained by saphenous vein endothelium before grafting predicts early graft attrition after off-pump coronary artery bypass graft surgery. METHODS: Intraoperative graft flow, platelet function, and endothelial integrity were analyzed in 125 patients undergoing off-pump coronary artery bypass graft surgery. Endothelial integrity was assessed in an excess vein segment from each graft using immunohistochemistry (CD31 staining). Platelet function was monitored just before and immediately after revascularization and on postoperative days 1 and 3 using whole blood aggregometry, thrombelastography, and platelet activated clotting time. Platelet activation was monitored using flow cytometry. Intraoperative conduit blood flow, measured by transit time ultrasonography, was used to detect and rectify anastomotic problems. Early graft patency was determined on postoperative day 5 using gated multichannel computed tomography angiography. RESULTS: In 106 patients undergoing postoperative computed tomography evaluation, 10 vein grafts in 10 patients were discovered to have developed early thrombosis, representing 4% (10 of 217) of all vein grafts. Endothelial integrity was 10.75% +/- 17.56% in 10 grafts that failed early compared with 51.45% +/- 36.29% in patent grafts (p = 0.04). Perioperative platelet function and graft flow did not differ significantly between the two groups. CONCLUSIONS: Although endothelial disruption predicts early failure of bypass grafts, the importance of a hypercoaguable state and low graft flow as a cause of early graft thrombosis after off-pump coronary artery bypass graft surgery was not supported by our preliminary results. A means to assess, prevent, and treat intraoperative vein graft damage will likely improve early graft patency.

Aged↗

PubMed2005

Platelet function tests predict bleeding and thrombotic events after off-pump coronary bypass grafting.

OBJECTIVE: A balanced coagulation system after cardiac surgery minimizes bleeding and thrombotic events. However, the best method to monitor this balance has not been established. We used a series of tests of coagulation and platelet function to define the risk of bleeding and thrombotic events after OPCAB. METHODS: In 76 patients, routine coagulation tests (i.e. prothrombin time, fibrinogen level, d-dimer, and platelet count), thrombelastography, and whole blood aggregometry were obtained perioperatively and on days 1 and 3 after OPCAB. Intra- and postoperative blood loss was determined. Early patency of venous bypass grafts was determined using CT angiography (Philips Medical, Corp.). RESULTS: Chest tube output and red cell volume loss at 24 h were 952+/-475 and 190+/-115 ml, respectively. Early graft failure developed in eight patients. Perioperative changes in routine coagulation tests showed no correlation with either bleeding or thrombosis. However, perioperative decline in platelet function as assessed by the area under the impedance curve for whole blood aggregometry correlated with intraoperative blood loss (R=0.42, P<0.05). A perioperative decline in the maximum amplitude of the thrombelastography trace showed a significant correlation with 24h hemoglobin loss (R=0.45, P<0.05). Compared to those with all patent grafts, patients with early graft failure demonstrated a reduction in platelet sensitivity to aspirin by both thrombelastography and aggregometry on day 3. CONCLUSIONS: In contrast to standard coagulation testing, platelet function predicted both bleeding and thrombosis after OPCAB. Titration of perioperative platelet function according to these tests may minimize thrombosis without increasing bleeding.

Aged↗

PubMed2005

Hypercoagulability affecting early vein graft patency does not exist after off-pump coronary artery bypass.

OBJECTIVE: Hypercoagulability may compromise the patency of bypass grafts. The authors hypothesized that perioperative in vitro platelet responses to varying agonists (eg, thrombin, platelet activating factor, collagen, adenosine diphosphate) correlate with early graft thrombosis after off-pump coronary artery bypass grafting (OPCAB). DESIGN AND PARTICIPANTS: Prospective study of 78 OPCAB patients with 151 venous bypass grafts treated with perioperative aspirin and intraoperative heparin (250 U/kg). SETTING: Tertiary, academic medical center. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hypercoagulability, defined by TEG (maximum amplitude [MA]>70 mm), whole-blood aggregometry (>15 ohms after 5 mcl/mL collagen) or hemoSTATUS (Ch5CR>0.5), was serially assessed around OPCAB. An immediate decline in platelet function after surgery and on postoperative day 1 returned to normal by postoperative day 3 in most patients. Graft blood flow was analyzed intraoperatively, and vein biopsies were analyzed for endothelial disruption. Graft patency was assessed by multichannel computed tomography coronary angiography on postoperative day 5. No differences in any of the platelet function assays were noted for the 8 patients with graft thrombosis (n=8 grafts) versus the 68 patients with all patent grafts (n=129 grafts). Ten patients developed a rise in platelet function postoperatively >1 SD above baseline; only 1 developed graft thrombosis (p=not significant v patients with normal platelet function). CONCLUSIONS: OPCAB is not associated with a significant activation in postoperative platelet function. This study suggests that if hypercoagulability exists after OPCAB, it is not involved in the pathogenesis of arterial thrombotic events such as early bypass graft failure.

Aged↗

PubMed2004

Optimizing donor heart outcome after prolonged storage with endothelial function analysis and continuous perfusion.

BACKGROUND: By minimizing tissue ischemia, continuous perfusion (CP) during organ transport may increase the safety of "marginal donors." My colleagues and I investigated whether an analysis of donor heart viability predicts recovery of grafts challenged with a 24-hour preservation interval. METHODS: Dog hearts underwent cold static storage (CS) for 8 hours (n = 8) or 24 hours (n = 2) or CP for 24 hours with cold asanguinous, oxygenated solution (n = 8). Myocardial systolic and diastolic function and oxygen and lactate consumption were assessed at base line, during CP, and after Langendorff blood reperfusion. Base line endothelial function was evaluated by the percentage transcoronary change ([coronary sinus - aorta]/aorta) in myeloperoxidase and by platelet function and coronary flow reserve after 20 seconds of coronary artery occlusion. During CP, the endothelium was assessed by transcoronary protein release and coronary resistance. Edema was assessed by weight gain and histology. RESULTS: Base line systolic and metabolic functions showed no relation to post-Langendorff function. Compared with CS, CP resulted in a greater recovery in systolic function (87% +/- 35% vs 65% +/- 15% of baseline; p = 0.05) and a shorter interval required for lactate consumption to exceed production (7.0 +/- 6.8 minutes vs 15.0 +/- 8.9 minutes; p = 0.06). Endothelial function was heterogeneous: coronary flow reserve, 2.7 +/- 0.7; percentage change in myeloperoxidase, -8.4% +/- 6.8%; and change in platelet function, 4.3% +/- 3.5%, as determined by thromboelastography angle at base line. Protein release during CP for 24 hours was 8.3 +/- 7.1 g. Two factors predicted more than 75% systolic pressure generation recovery: use of CP and normal endothelial function (p = 0.05; Fisher's exact test). However, CP led to edema according to histology, weight gain (72 +/- 29 g), and impaired diastolic function versus CS (end-diastolic pressure-volume relationship, 1.4 +/- 0.4 mm Hg/mL vs 0.8 +/- 0.3 mm Hg/mL; p = 0.08). CONCLUSIONS: Better systolic function despite 16 hours' more preservation than cold storage corroborates the idea that CP supports aerobic metabolism at physiologically important levels. Viability analysis focused on endothelial function and identified organs that were able to tolerate this 24-hour preservation interval.

Aerobiosis↗

PubMed2004

Virchow triad, but not use of an aortic connector device, predicts early graft failure after off-pump coronary bypass.

The risk of early thrombosis of coronary artery bypass (CAB) grafts may be increased after off-pump CAB, particularly after the use of an aortic connector device (ACD) to perform the proximal aortosaphenous anastomosis. We have been investigating tools that quantify the risk of early vein graft thrombosis after off-pump CAB on the basis of the Virchow triad of hypercoagulability, endothelial disease, and low conduit flow. These tools were applied in this prospective trial of a heterogeneous group of patients with varying degrees of aortic disease and who received the Symmetry ACD. After controlling for the Virchow risk factor triad, we hypothesized that the ACD does not independently influence graft thrombosis. There was no statistically significant difference in the early thrombosis rates of vein grafts connected with an ACD versus hand-sewn grafts (6.7% versus 6.5%). We found a wide range of graft flow measurements, platelet function, and vein endothelial phenotypes in patients with traditionally hand-sewn vein grafts and with grafts connected with an ACD in patients with a wide range of ascending aortic atherosclerosis. The perioperative combination of platelet hyperreactivity, marginal graft flow, and endothelial disease proved to be highly predictive of early graft failure as seen with postoperative computed tomographic angiography.

Aorta↗